Associations between both genetic and environmental biomarkers and lung cancer: evidence of a greater risk of lung cancer in women smokers

This molecular epidemiologic case-control study of lung cancer incorporatedthree complementary biomarkers: the glutathione S- transferase M1 (GSTM1)null genotype, a potential marker of susceptibility, and polycyclicaromatic hydrocarbon-DNA adducts (PAH- DNA) and sister chromatid exchanges(SCE), both indicators of environmentally induced genetic damage.Associations between biomarkers and lung cancer were investigated, as werepossible gene-environment interactions between the GSTM1 null genotype andtobacco smoke exposure. Subjects included 136 primary non-small cell lungcancer surgical patients and 115 controls at the Columbia PresbyterianMedical Center. Questionnaire and Tumor Registry data, pre-treatment bloodsamples and biomarker measurements on blood were obtained. Overall, GSTM1null genotype was significantly associated with lung cancer [odds ratio(OR) = 2.04, 95% confidence interval (CI) = 1.13-3.68]. ORs for GSTM1 andlung cancer were significant in females (2.50, 1.09-5.72) and smokers(2.25, 1.11-4.54) and not significant in males (1.4, 0.58-3.38) andnon-smokers (0.88, 0.18-4.33). However, ORs for males versus females andsmokers versus non-smokers did not differ significantly. The OR for GSTM1and lung cancer in female smokers was 3.03 (1.09- 8.40), compared with 1.42(0.53-4.06) in male smokers. In contrast to PAH-DNA adducts in leukocytes,SCE did not differ between cases and controls. Neither biomarker differedsignificantly between the two GSTM1 genotypes. The combined effect ofelevated PAH-DNA adducts and GSTM1 genotype on case-control status (16.19,1.2-115) appeared multiplicative. Results suggest that the effect of theGSTM1 null genotype is greatest in female smokers, which is consistent withother evidence that indicates that women are at higher risk of lung cancerthan males, given equal smoking. Persons with both the GSTM1 deletion andelevated PAH-DNA adducts may represent a sensitive subpopulation withrespect to carcinogens in tobacco smoke and other environmental media.